RESEARCH ARTICLE
An Elevated Peripheral Blood Monocyte-toLymphocyte Ratio Predicts Poor Prognosis in Patients with Primary Pulmonary Lymphoepithelioma-Like Carcinoma Liang Wang1,2☯, Wen Long1,3☯, Peng-fei Li1,4☯, Yong-bin Lin1,5, Ying Liang1,6* 1 State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People’s Republic of China, 2 Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China, 3 Department of Nuclear Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China, 4 Department of Pediatric Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China, 5 Department of Thoracic Surgery, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China, 6 Department of Medical Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China ☯ These authors contributed equally to this work. *
[email protected] OPEN ACCESS Citation: Wang L, Long W, Li P-f, Lin Y-b, Liang Y (2015) An Elevated Peripheral Blood Monocyte-toLymphocyte Ratio Predicts Poor Prognosis in Patients with Primary Pulmonary LymphoepitheliomaLike Carcinoma. PLoS ONE 10(5): e0126269. doi:10.1371/journal.pone.0126269 Academic Editor: Fan Yang, Peking University People Hospital, CHINA Received: January 13, 2015 Accepted: March 31, 2015 Published: May 7, 2015 Copyright: © 2015 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper. Funding: LW received grant support from National Natural Science Foundation of China (contract/grant number: 81400159, http://www.nsfc.gov.cn/), and Medical Research Foundation of Guangdong Province (grant number: B2014158, http://www. medste.gd.cn/); YL received grant support from Department of Health of Guangdong Province (grant number: B2009089, http://www.medste.gd.cn/).
Abstract Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer. In this study, we retrospectively reviewed the data from 74 consecutive patients with pulmonary LELC and investigated the prognostic value of pretreatment monocyte-to-lymphocyte ratio (MLR). The cut-off value determined by ROC curve for MLR was 0.262. According to this cut-off value, 36 (48.6%) patients had lower MLR value ( = 0.262) were significantly associated with poor OS and PFS. In a multivariate Cox regression model that included stage, LDH and MLR level, all of these three factors were found to be independent prognostic factors for both PFS and OS. In patients who received radical surgery, MLR level remained significantly correlated with OS and PFS. In conclusion, we firstly demonstrated that pretreatment MLR can be used as a useful independent prognostic marker in patients with pulmonary LELC, and might guide us to optimize the treatment strategies. However, due to the relatively rarity of this disease and the limitation of a retrospective study, further prospective studies performed in multicenter are necessary to validate the prognostic value of MLR in pulmonary LELC.
PLOS ONE | DOI:10.1371/journal.pone.0126269 May 7, 2015
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Prognostic Role of MLR in Pulmonary LELC
Competing Interests: The authors have declared that no competing interests exist.
Introduction Primary pulmonary lymphoepithelioma-like carcinoma (LELC), a rare type of non-small cell lung cancer (NSCLC), was firstly reported by Begin et al [1] in 1987, and is categorized as a subtype of large cell carcinoma [2]. It is reported to be closely related to the infection of Epstein-Barr virus (EBV), and has similar histology to nasopharyngeal carcinoma [3], which is a type of undifferentiated carcinoma with predominant lymphocytic infiltration. Recent studies have found that patients with pulmonary LELC have significantly better prognosis than other types of NSCLC [4]. However, due to the rarity of this disease, treatment strategy is still controversial. Radical surgery is usually performed for early stage disease, and combination of chemotherapy and radiotherapy has been used in locally advanced or metastatic disease. In recent years, increasing case reports or cohort studies have been published, mainly focusing on the treatment approaches or exploration of driving genes, butno large cohort studies have ever been reported to investigate prognostic factors for pulmonary LELC. Thus, it is of great importance to find some valuable prognostic factors to guide treatments. It is now widely recognized that cancer-associated inflammation is very common in tumor progression and associated with survival in variety of cancers [5]. Lymphocytes and monocytes are the main type of immune cells involved in the inflammatory process and have been demonstrated to be associated with the prognosis of many malignancies [6–9]. Recently, the pretreatment lymphocyte-to-monocyte ratio (LMR) or monocyte-to-lymphocyte ratio (MLR) has been shown to be a prognostic factor for clinical outcomes in diffuse large B-cell lymphoma[8] and lung cancers[10]. Therefore, we hypothesized that MLR may also play an important role in pulmonary LELC. We performed a large retrospective cohort study on patients with pulmonary LELC and investigated the prognostic value of pretreatment MLR. To our knowledge, this is the first large-scale study on the association between MLR and LELC.
Materials and Methods Patients 74 consecutive patients with pulmonary LELC from January 2001 to December 2013 were enrolled in this study. As previously reported [4], patients with negative Epstein-Barr virus (EBV)-encoded RNA (EBER) staining were excluded in this study. Nasopharyngoscopy or PET-CT was done to rule out lung metastasis from nasopharyngeal carcinoma. Sun Yat-sen University Cancer Center Research Ethics Board has approved us to use the data in this study, and written informed consent for use and publication of patients’ medical information was obtained from all patients at their first visit. We restaged all cases based on the American Joint Committee on Cancer (AJCC) staging system (the 2007 TNM Classification of Malignant Tumors)[11], and both clinical and pathological characteristics were reviewed. The MLR was calculated based on the whole blood cell counts at diagnosis. Treatment response was evaluated after at least 2 cycles of chemotherapy.
Statistical analysis Receiver operating characteristic (ROC) curve was performed to search the best cut-off value for MLR to stratify patients at a high risk of death (using SPSS version 19 statistical software). In this ROC curve, the point with the maximum sensitivity and specificity was selected as the best cut-off value. Progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan–Meier method, while log-rank test was used for comparison. OS was calculated from the date of diagnosis to the date of death from any cause, and was censored at the date of last follow-up interview. PFS was calculated from the date of diagnosis to the date of disease
PLOS ONE | DOI:10.1371/journal.pone.0126269 May 7, 2015
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Prognostic Role of MLR in Pulmonary LELC
Table 1. Clinical characteristics of 74 patients with pulmonary LELC. Parameters Gender Age Smoking history Stage Hemoglobin level Serum LDH level Serum albumin level Tumor size MLR* Treatment
Outcome
Number of patients (N = 74)
Percentage (%) 47.3
Male
35
Female
39
52.7
= 60
14
18.9
No
58
78.4
Yes
16
21.6
I-II
42
56.8
III-IV
32
43.2
